Male sterile mutants of the mouse provide models for analysis of sperm differentiation and function which can also lead to greater understanding of reproductive dysfunction and infertility. The causes and consequences of structural abnormalities in spermatozoa from mice bearing male sterile mutations will be studied from three different yet coherent perspectives. First, to determine if genes causing male sterility are acting in germ cells or in somatic cells, mouse chimeras will be constructed bearing both genetically male sterile and normal cells in the testis. Determination of fertility and analysis o any progeny from these mice will clarify the site of gene action in causing sterility. Second, because it is not known whether the sterile mutants are sterile as a direct consequence of sperm abnormalites, experiments will assess the relative success f sperm both from sterile mice and from fertile mice in reaching the site of fertilization after natural mating, artificial insemination, or fertilization in vitro. These experiments will provide data both on the ability of sperm from sterile mutants to reach the site of fertilization and on the relative success of structurally abnormal sperm from either sterile mice or fertile mice in reaching the fertilization site. This should allow determination of whether sterility can be a consequence of the manufacture of abnormally shaped sperm. Finally, since previous chimera studies have indicated extra-testicular action of genes causing male sterility, radioimmunoassay techniques will be employed to measure levels of reproductive hormones (FSH, LH, prolactin, and testosterone) in genetically male sterile mice. These studies also will help clarify the site of action of genes causing male sterility. The results of these different approaches to analysis of genetic male sterility will enhance our understanding of the genetic and cellular mechanisms controlling sperm differentiation and function.